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Elected as EA President in 2253, Santiago was a great supporter of the Babylon Project, an initiative inherited from his predecessor Elizabeth Levy, persevering despite the first four stations being destroyed or disappearing without a trace. When B5 finally went on line, Santiago allowed the Minbari to choose Jeffrey Sinclair as the station's commander, though left orders in place that if anything happened to Sinclair, CaptainJohn Sheridan would take his place.[1] Due to the support of the Minbari, Santiago gave Sinclair complete authority over all matters on the station.[2]

In 2258, Santiago defeating challenger Marie Crane and was re-elected for a second term with a promise to cut the budget and to keep Earth out of war. His agenda includes creating a closer relationship with the Mars colony and preserving Earth cultures in the face of growing non-Terran influences.[3]

In June, Santiago visited Babylon 5, presenting the station with a new squadron of Starfuries and attended a reception with all of the station's alien Ambassadors. He concluded his address by inviting the alien governments to work more closely with Earth, a position certain to cause much controversy back home.[4]

Santiago got word of the Mars Resistance and, though initially unwilling, eventually authorized the use of force to quell the attackers. In a separate incident, Santiago confirmed with Senator Hidoshi that Sinclair had authority over B5 and could not be overridden by Earthforce.[2]

In late December 2258, Santiago departed Mars on Earthforce One, on a good will tour of the outer colonies. On New Year's Day 2259, Santiago was anticipated to give a major policy speech concerning human/alien relations over the remainder of his term. He never made the speech as ten minutes after he was due to go live, Earthforce One exploded - live on ISN - off the Iotransfer point in what a subsequent investigation determined was an accident involving the ship's fusion reactor.[5]

Following confirmation of Santiago's death, Vice PresidentMorgan Clark - who had conveniently disembarked Earthforce One at Mars claiming to be suffering from a viral infection - was sworn in as the new EA President in a ceremony aboard Earthforce Two en route back to Earth. Clark gave a speech announcing that he intended to create the world that Luis Santiago would have wanted, beginning by focusing on the needs of humans and "prepare them for the tasks ahead."[5]

Clark's role in the assassination was later exposed,[6] but he had been consolidating dictatorial power since taking office, and he illegally declared martial law and dissolved the Earth Senate before the evidence could be acted upon.[7] By the time it became possible to investigate Clark's role in the assassination, he had committed suicide, leaving only co-conspirators to prosecute, and it had become merely the first of countless crimes committed by the administration.[8][9]

Although he featured in three episodes of Season One, Santiago was never actually seen in the flesh, showing up only as an off camera voice in ("Survivors") and as file photos on ISN in both ("Midnight on the Firing Line") and ("Chrysalis").